A Dose Finding Study of GSK716155 Versus Placebo in the Treatment of Type 2 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 215
- 试验地点
- 30
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging study evaluating the dose response, efficacy and safety of subcutaneously injected GSK716155 (albiglutide) in Japanese subjects with type 2 diabetes mellitus.
详细描述
This is a Phase IIb, randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging, superiority study evaluating the dose response, efficacy and safety of weekly and every other week subcutaneously injected GSK716155 (albiglutide) in subjects with type 2 diabetes mellitus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject with a historical diagnosis of type 2 diabetes mellitus who is currently treated with diet and exercise only or one OAD
- •BMI ≥18 kg/m2 and <35 kg/m2 at Screening
- •HbA1c between 7.0% and 10.0%, inclusive
- •Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)
- •Female subjects of childbearing potential must be practicing adequate contraception .
- •Able and willing to monitor his/her own blood glucose concentrations with a home glucose monitor.
- •Able and willing to provide written informed consent
排除标准
- •Diagnosis of type 1 diabetes mellitus
- •Uncorrected thyroid dysfunction
- •Previous use of insulin within one month prior to screening, or more than seven total days of insulin treatment within three months prior to screening
- •Clinically significantly cardiovascular and/or cerebrovascular disease including, but not limited to the following:
- •Previous history of stroke or transient ischemic attack
- •Active, unstable coronary heart disease within the past six months before Screening
- •Documented myocardial infarction within one year before Screening
- •Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary stent placement, or coronary artery bypass graft surgery within one year before Screening
- •Unstable angina
- •Clinically significant arrhythmia or valvular heart disease
- •Current heart failure NYHA class II to IV
- •Resting systolic pressure >160 mm Hg or diastolic pressure >95 mm Hg at Screening
- •ECG criteria at Screening
- •Heart rate: <40 and >110 bpm
- •PR interval: <120 and > 210 msec
- •QRS interval: <70 and >120 msec
- •QTc interval (Bazett): >450 msec or >480 msec with bundle branch block
- •Fasting triglyceride level >400 mg/dL at Screening
- •AST or ALT >2xULN, ALP and bilirubin >1.5xULN (except known Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin)
- •If female, is currently lactating, within 6 weeks post-partum, pregnant, or actively trying to become pregnant
- •Has significant renal disease as manifested by one or more of the following:
- •Creatinine clearance at screening <60 mL/min (calculated by Cockcroft-Gault formula) at Screening
- •Known loss of a kidney either by surgical ablation, injury or disease level
- •A hemoglobinopathy that may affect determination of HbA1c level
- •History of treated diabetic gastroparesis
- •History of significant gastrointestinal surgery, including gastric bypass and banding, or surgeries thought to significantly affect upper gastrointestinal function
- •Current ongoing symptomatic biliary disease or history of acute/chronic pancreatitis.
- •Lipase and amylase at Screening > ULN
- •Severe diabetic neuropathy, preproliferative retinopathy or proliferative retinopathy, history of ketoacidosis or hyperosmolar coma
- •History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)
- •Acute or chronic history of liver disease, positive hepatitis B surface antigen (HBsAg) or positive hepatitis C testing at Screening
- •Current and history of alcohol or substance abuse
- •Clinically significant anaemia or any other abnormal haematological profile that is considered by the investigator to be clinically significant
- •Prior use of a GLP-1 analog
- •Known allergy to any formulation excipients, or Baker's yeast, or history of drug, or other allergy which, in the opinion of the responsible study physician, contradicts participation
- •History of or family history of medullary carcinoma of the thyroid.
- •History of or family history of multiple endocrine neoplasia type 2
- •Receipt of any investigational drug within the 12 weeks before Screening
研究组 & 干预措施
placebo
once weekly subcutaneous injection of placebo to match albiglutide
干预措施: placebo (Biological)
albiglutide 30mg every other week
subcutaneous injection of 30mg albiglutide every other week
干预措施: albiglutide (Biological)
albiglutide 30mg weekly
once weekly subcutaneous injection of albiglutide 30mg
干预措施: albiglutide (Biological)
albiglutide 15mg weekly
once weekly subcutaneous injection of albiglutide 15mg
干预措施: albiglutide (Biological)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
时间窗: Baseline and Week 16
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 16 minus the value at Baseline. Based on Analysis of Covariance (ANCOVA): Change = treatment + Baseline HbA1c + prior therapy. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.
次要结局
- Change From Baseline in Body Weight at Week 4, 8, 12, and 16(Baseline; Week 4, Week 8, Week 12, and Week 16)
- Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16(Week 4, Week 8, Week 12, and Week 16)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16(Baseline; Week 4, Week 8, Week 12, and Week 16)
- Mean Absorption Rate of Albiglutide(Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24)
- Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16(Baseline; Week 4, Week 8, Week 12, and Week 16)
- Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG(Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24)
- Mean Clearance of Albiglutide(Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24)
- Mean Volume of Distribution of Albiglutide(Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24)